Metagenomic study of diet-dependent interaction between gut microbiota and host in infants
Gut microbiota and the host share a mutualistic relationship, in which the survival of gut microbiota relies on nutrients from the host, while the health and well-being of the host is strongly affected by the microbiota, especailly by its functional composition. Microbial colonization plays an essential role in infants in directing neonatal intestine and immune system development. Overview Schwartz and his colleagues conducted a simultaneous study of the gut microbiome and host epithelial transcriptiome of three-month-old exclusively breast- and formula-fed infants. They found that diet difference can affect, via colonization, the host expression of genes associated with innate immune system. Backgound Human intestine is lined by epthelial cells. These cells not only process nutrient, but also play important role in the first-line defense againt food antigens and pathogens. At birth, the infant's intestinal track is functionally immature and sterile, hence, the early neonatal period is a critical phase for intestinal degestive development and colonization by commensal microbiota. Since colonization by commensal microbiota is essential for neonatal intestinal development, it is suggested that epithelial cells and the microbial ecosystem are modulated by diet. Procedure A total of 12 infants were recruited for the research (6 breast fed and 6 formula fed). Since about one sixth of intestinal epithelial cells are exfoliated everyday, and excreted as feces, stool samples of the 12 infants were collected. mRNA was isolated from exfoliated host (epithelial) cells, they it was used for determining the gene combination that best distinguishes the feeding group. The authors then conducted a simultaneous examination of both host and microbial responses to dietary/environmental components in the early neonatal period. Results 459 intestinal-biology related genes and 660 immunity and defense-related genes were tested for differential expression between breast fed and formula fed infants using a permutation test with a false discovery rate (FDR, q value) multiple testing correction, and those having q valuse less than 0.2 (149 intestinal-biology related and 191 immunity and defense-related genes) were subjected to independent gene ontology analysis (GO). Results suggested that genes expected a priori is responsive to diet were enriched for differential expression. Taxonomical analysis results demonstrated that all formula fed infants microbiota is homogeneous in phylum level distribution, about 40% Firmicutes, 40% Actinobacteria, and 20% proteobacteria; while in breast fed infants are more heterogenous in phylum composition (each breast fed infants showed different phylum domination). The authors also conducted functional analysis to investigate the effect of diet variation in gut metagenome by aligning shotgun sequenced data against SEED subsystems database. Genes in SEED database is annotated using a three-level biological-function ontology, where level 1 represents the most general and level 3 represents most specific. Permutation test results showed that the virulence of the microbiota were potentially responsive characteristics with respect to diet compositon. Furthermore, the relative proportion of level 2 genes within level 1 virulence category differed between breast and formula fed infants. Canonical correlation assays were conducted to examine the multivariate structure between virulence characteristics of the microbiota (resistance to antibiotic and toxic compounds, Type III, Type IV, ESAT secretion systems, and iron scavenging mechanisms) and host transcriptome data sets. Each gene triples (selected from the transcriptome data set) analyzed with metagenomic virulence variables contains three canonical correlations. Results from first and second canonical correlations between host gene sets and microbial virulence characteristics inditified 11 host genes that are associated with immune response, whose expression differed between breast and formula fed infants. They are VAV2 (angiogenesis), ALOX5 (inflammatory factor), SP2 (transcription factor), BPIL1 (bacteriocidal), DUOX2 (peroxidase generation), KLRF1 (cytotoxicity), IL1A (inflammatory response), AOC3 (vascular adhesion), NDST1 (infalmmation and mucosaldefense), REL (intestine proliferation and apoptotic homeostasis) and TACR1 (gut motility). Discussion and Conclusion In human infants, there is a stronger trophic response to human milk than formula, this demonstrates that human milk is important for gastrointestinal development. The third section of Result showed that microbiome characteristics exhibit differential sensitivity to breast milk comparing to formula. Furthermore, the 11 identified genes showed evidence of a multivariate relationship with microbiome virulence and invasiveness characteristics, suggesting that these intestinal genes are important in microbiome regulatory pathways and integrative gut development process. In summary, the composition of neonatal microbiota is influenced by diet. Reference 1. Schwartz, S., et al. Genome Biology (2012) 13(4): r32 A Metagenomic Study of diet-dependent interaction between gut microbiota and host in infants reveals differences in immune response http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3446306/#!po=30.3571 2. P, Chopra., et al. Stem Cells Dev (2010) 19(1): 131-42 Intestinal epithelial cells in vitro http://www.ncbi.nlm.nih.gov/pubmed/19580443 3. Stadnyk, A., et al. eLS (2009) DOI: 10.1002/9780470015902.a0003816.pub2, Intestinal Epithelial Cells: Immunological Aspects http://www.els.net/WileyCDA/ElsArticle/refId-a0003816.html